Field of Invention
The present invention relates to a peptide and application thereof. More particularly, the present invention relates to a short peptide-based therapeutic agent, a medicinal composition including the same and a method for inhibiting activities of cancer cells by using the aforementioned medicinal composition.
Description of Related Art
Among the cancer patients suffering from metastatic or malignant tumors that are unlikely eradicated by surgical intervention, the majority of cancer patients receive chemotherapy after surgical intervention of the primary tumor site, for inhibiting the proliferation and metastasis of potential cancel cells. However, even when chemotherapy appears successful, cancer patients still face the risk of recurrence of the same or a drug-resistant cancer. The patients with recurrent cancers, especially the ones with drug-resistant cancers during the chemotherapy, suffer higher risk due to faster metastases occurred in the recurrent cancers.
In the case of carcinomas, it is found that the cancer cells can stimulate the tumor microenvironment to generate various inflammatory factors, white blood cells, overgrown blood vessels, proteases and so on. The cancer-related chronic inflammation also influences the proliferation, metastasis and invasion of cancer cells; however, the causes and the detailed mechanisms of the cancer-related chronic inflammation are still unclear.
In addition to the cancer-related chronic inflammation, in other researches, the tumor microenvironment is also highly related to metastasis and chemoresistance. The tumor microenvironment is constituted of a heterogenous population of stromal cells and other different types of cells, for protecting the tumor, enabling cancer cells to evade and resist the attack of immune cells, thereby conferring drug resistance to the cancer cells.
Besides, based on previous studies of the inventors of the present invention, the decrease of CCAAT/enhancer binding protein delta (CEBPD) of stromal cells contributes to cancer progression. That is to say, the reactivation of CEBPD may be helpful to suppress the cancer cell proliferation.
Fibroblasts and macrophages in the stroma surrounding the tumor are activated by CEBPD and induced to generate secretory factors, including pentraxin-related protein (PTX3). PTX3 has activities of angiogenesis, metastasis and invasion of breast cancer cells, lung cancer cells, and nasopharyngeal cancer cells. In addition, when CEBPD of the cells in the tissue surrounding the tumor is activated, it will facilitate the tumor metastasis and the generation of drug-resistant cancer cells during chemotherapy, all of which has been evidenced by the inventors of the present invention.
There are some commercially available small-molecule anti-cancer drugs, for examples, cis-diammine dichloroplatinum (II) (CDDP; the trade name of Cisplatin), paclitaxel (the trade name of Taxol), 5-Fluorouracil (5-FU) and the like. However, in recent researches, it is found that those commercial small-molecule anti-cancer drugs can activate the CEBPD in fibroblasts and macrophages, resulting in poor cancer treatment such as drug resistance and fast metastasis of cancer cells.
Accordingly, there is an urgent need to develop a small-molecule anti-cancer drug, for overcoming the problems of drug resistance and fast metastasis occurred in conventional small-molecule anti-cancer drugs.